Large numbers of
hormone replacement therapies (HRTs) are available for the treatment of menopausal symptoms. It is still unclear whether some are more deleterious than others regarding
breast cancer risk. The goal of this study was to assess and compare the association between different HRTs and
breast cancer risk, using data from the French E3N cohort study. Invasive
breast cancer cases were identified through biennial self-administered questionnaires completed from 1990 to 2002. During follow-up (mean duration 8.1 postmenopausal years), 2,354 cases of invasive
breast cancer occurred among 80,377 postmenopausal women. Compared with HRT never-use, use of
estrogen alone was associated with a significant 1.29-fold increased risk (95% confidence interval 1.02-1.65). The association of
estrogen-
progestagen combinations with
breast cancer risk varied significantly according to the type of
progestagen: the relative risk was 1.00 (0.83-1.22) for
estrogen-
progesterone, 1.16 (0.94-1.43) for
estrogen-
dydrogesterone, and 1.69 (1.50-1.91) for
estrogen combined with other
progestagens. This latter category involves
progestins with different physiologic activities (androgenic, nonandrogenic, antiandrogenic), but their associations with
breast cancer risk did not differ significantly from one another. This study found no evidence of an association with risk according to the route of
estrogen administration (oral or transdermal/percutaneous). These findings suggest that the choice of the
progestagen component in combined HRT is of importance regarding
breast cancer risk; it could be preferable to use
progesterone or
dydrogesterone.